盖塔病毒研究进展

盖塔病毒(Getah virus,GETV)是披膜病毒科甲病毒属的虫媒病毒.GETV感染已在多种脊椎动物中发现,包括人类、猴子、鸟类、猪、马和其他哺乳动物.GETV感染可导致马出现发热、全身皮疹和腿水肿,仔猪关节炎和母猪生殖障碍等.目前GETV在世界范围内流行较为广泛,近年来逐步在猪群中暴发,导致部分猪场经济损失严重,同时在中国感染的宿主范围不断扩大,相继出现了第一例狐狸、猪、马、牛感染.本文对GETV的分子结构、致病机制、宿主范围、流行状况以及疫苗研究进展进行综述,以期为我国GETV的深入研究及防控工作提供一定思路.     

气候变化对中国马可波罗盘羊适宜生境的潜在影响

气候变化可能造成生物多样性下降和物种灭绝。开展气候变化对濒危野生动物分布格局影响的研究,对识别野生动物优先保护区、制定相关保护策略具有重要价值。本研究基于2017—2018年在新疆塔什库尔干野生动物自然保护区野外调查获得的马可波罗盘羊(Ovis ammon polii)分布位点,采用最大熵模型预测了气候变化下其适宜生境分布格局动态。结果表明: 马可波罗盘羊当前的适宜生境主要分布于保护区西北部,温度是影响其适宜生境分布的关键因子。在中、高排放浓度(RCP4.5和RCP8.5)下,未来2050s和2070s两个时期马可波罗盘羊的适宜生境面积主要呈下降趋势,适宜生境丧失率高达40.5%;丧失的适宜生境主要位于低海拔区域,高海拔区域的适宜生境面积相应增加;由低海拔向高海拔转移的适宜生境面积随温室气体排放浓度升高而增加。从质心转移结果来看,其适宜生境主要向西(即马可波罗盘羊主要分布国塔吉克斯坦)迁移。     

Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls

The HIV-1 broadly neutralizing Ab (bnAb) 2F5 has been shown to be poly-/self-reactive in vitro, and we previously demonstrated that targeted expression of its VDJ rearrangement alone was sufficient to trigger a profound B cell developmental blockade in 2F5 V(H) knockin (KI) mice, consistent with central deletion of 2F5 H chain-expressing B cells. In this study, we generate a strain expressing the entire 2F5 bnAb specificity, 2F5 V(H) × V(L) KI mice, and find an even higher degree of tolerance control than observed in the 2F5 V(H) KI strain. Although B cell development was severely impaired in 2F5 V(H) × V(L) KI animals, we demonstrate rescue of their B cells when cultured in IL-7/BAFF. Intriguingly, even under these conditions, most rescued B cell hybridomas produced mAbs that lacked HIV-1 Envelope (Env) reactivity due to editing of the 2F5 L chain, and the majority of rescued B cells retained an anergic phenotype. Thus, when clonal deletion is circumvented, κ editing and anergy are additional safeguards preventing 2F5 V(H)/V(L) expression by immature/transitional B cells. Importantly, 7% of rescued B cells retained 2F5 V(H)/V(L) expression and secreted Env-specific mAbs with HIV-1-neutralizing activity. This partial rescue was further corroborated in vivo, as reflected by the anergic phenotype of most rescued B cells in 2F5 V(H) × V(L) KI × Eμ-Bcl-2 transgenic mice and significant (yet modest) enrichment of Env-specific B cells and serum Igs. The rescued 2F5 mAb-producing B cell clones in this study are the first examples, to our knowledge, of in vivo-derived bone marrow precursors specifying HIV-1 bnAbs and provide a starting point for design of strategies aimed at rescuing such B cells.     

Cutting Edge: Immunological consequences and trafficking of human regulatory macrophages administered to renal transplant recipients

Regulatory macrophages (M regs) were administered to two living-donor renal transplant recipients. Both patients were minimized to low-dose tacrolimus monotherapy within 24 wk of transplantation and subsequently maintained excellent graft function. After central venous administration, most M regs remained viable and were seen to traffic from the pulmonary vasculature via the blood to liver, spleen, and bone marrow. By 1 y posttransplantation, both patients displayed patterns of peripheral blood gene expression converging upon the IOT-RISET signature. Furthermore, both patients maintained levels of peripheral blood FOXP3 and TOAG-1 mRNA expression within the range consistent with nonrejection. It is concluded that M regs warrant further study as a potential immune-conditioning therapy for use in solid-organ transplantation. The results of this work are being used to inform the design of The ONE Study, a multinational clinical trial of immunomodulatory cell therapy in renal transplantation.     

Addressing Passive Smoking in Children

Background

A significant number of parents are unaware or unconvinced of the health consequences of passive smoking (PS) in children. Physicians could increase parental awareness by giving personal advice.

Aim

To evaluate the current practices of three Dutch health professions (paediatricians, youth health care physicians, and family physicians) regarding parental counselling for passive smoking (PS) in children.

Methods

All physicians (n = 720) representing the three health professions in Limburg, the Netherlands, received an invitation to complete a self-administered electronic questionnaire including questions on their: sex, work experience, personal smoking habits, counselling practices and education regarding PS in children.

Results

The response rate was 34%. One tenth (11%) of the responding physicians always addressed PS in children, 32% often, 54% occasionally and 4% reported to never attend to it. The three health professions appeared comparable regarding their frequency of parental counselling for PS in children. Addressing PS was more likely when children had respiratory problems. Lack of time was the most frequently mentioned barrier, being very and somewhat applicable for respectively 14% and 43% of the physicians. One fourth of the responders had received postgraduate education about PS. Additionally, 49% of the responders who did not have any education about PS were interested in receiving it.

Conclusions

Physicians working in the paediatric field in Limburg, the Netherlands, could more frequently address PS in children with parents. Lack of time appeared to be the most mentioned barrier and physicians were more likely to counsel parents for PS in children with respiratory complaints/diseases. Finally, a need for more education on parental counselling for PS was expressed.     

Adiponectin Protects Rat Myocardium against Chronic Intermittent Hypoxia-Induced Injury via Inhibition of Endoplasmic Reticulum Stress

Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders such as heart failure, hypertension, atherosclerosis, and arrhythmia and so on. Of the many associated factors, chronic intermittent hypoxia (CIH) in particular is the primary player in OSAS. To assess the effects of CIH on cardiac function secondary to OSAS, we established a model to study the effects of CIH on Wistar rats. Specifically, we examined the possible underlying cellular mechanisms of hypoxic tissue damage and the possible protective role of adiponectin against hypoxic insults. In the first treatment group, rats were exposed to CIH conditions (nadir O2, 5–6%) for 8 hours/day, for 5 weeks. Subsequent CIH-induced cardiac dysfunction was measured by echocardiograph. Compared with the normal control (NC) group, rats in the CIH-exposed group experienced elevated levels of left ventricular end-systolic dimension and left ventricular end-systolic volume and depressed levels of left ventricular ejection fraction and left ventricular fractional shortening (p<0.05). However, when adiponectin (Ad) was added in CIH + Ad group, we saw a rescue in the elevations of the aforementioned left ventricular function (p<0.05). To assess critical cardiac injury, we detected myocardial apoptosis by Terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) analysis. It was showed that the apoptosis percentage in CIH group (2.948%) was significantly higher than that in NC group (0.4167%) and CIH + Ad group (1.219%) (p<0.05). Protein expressions of cleaved caspase-3, cleaved caspase-9, and cleaved-caspase-12 validated our TUNEL results (p<0.05). Mechanistically, our results demonstrated that the proteins expressed with endoplasmic reticulum stress and the expression of reactive oxygen species (ROS) were significantly elevated under CIH conditions, whereas Ad supplementation partially decreased them. Overall, our results suggested that Ad augmentation could improve CIH-induced left ventricular dysfunction and associated myocardial apoptosis by inhibition of ROS-dependent ER stress.     

Development of a Finite Element Model of Decompressive Craniectomy

Decompressive craniectomy (DC), an operation whereby part of the skull is removed, is used in the management of patients with brain swelling. While the aim of DC is to reduce intracranial pressure, there is the risk that brain deformation and mechanical strain associated with the operation could damage the brain tissue. The nature and extent of the resulting strain regime is poorly understood at present. Finite element (FE) models of DC can provide insight into this applied strain and hence assist in deciding on the best surgical procedures. However there is uncertainty about how well these models match experimental data, which are difficult to obtain clinically. Hence there is a need to validate any modelling approach outside the clinical setting. This paper develops an axisymmetric FE model of an idealised DC to assess the key features of such an FE model which are needed for an accurate simulation of DC. The FE models are compared with an experimental model using gelatin hydrogel, which has similar poro-viscoelastic material property characteristics to brain tissue. Strain on a central plane of the FE model and the front face of the experimental model, deformation and load relaxation curves are compared between experiment and FE. Results show good agreement between the FE and experimental models, providing confidence in applying the proposed FE modelling approach to DC. Such a model should use material properties appropriate for brain tissue and include a more realistic whole head geometry.     

Drugs-Related Death Soon after Hospital-Discharge among Drug Treatment Clients in Scotland: Record Linkage,Validation, and Investigation of Risk-Factors

We validate that the 28 days after hospital-discharge are high-risk for drugs-related death (DRD) among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD), including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29–90 days, 91 days–1 year, >1 year since most recent hospital discharge versus ‘never admitted’. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0–1 versus 2+ days), and main discharge-diagnosis. We confirm SDMD clients’ high DRD-rate soon after hospital-discharge in 2006–2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever-injectors for 222/290. Hospital-discharge remains a period of increased DRD-vulnerability in 2006–2010, as in 1996–2006, especially for those with a history of injecting.     

Predicting the Effects of Endocrine Disrupting Chemicals on Fish Populations

This study evaluates the applicability and sensitivity of fish population dynamics modeling in assessing the potential effects of individual chemicals on population sustainability and recovery. Fish reproductive health is an increasingly important issue for ecological risk assessment following international concern over endocrine disruption. Life-history data from natural brook trout and fathead minnow populations were combined with effects data from laboratory-based studies, mainly concerning species other than brook trout and fathead minnows, to assess the likely impact of nonylphenol (NP) and methoxychlor (MXC) on brook trout (Salvelinus fontinalis) and fathead minnow (Pimephales promelas) population size. A delay differential equation (DDE) model with a 1-day timestep was used to predict the population dynamics of the brook trout and fathead minnows. The model predicts that NP, could enhance populations by up to 17% at a concentration of 30?µg l^?1 based on the results of reduction in survival and increased fecundity from life-cycle toxicity tests, however attempting to allow for growth reduction and its effect on fecundity results in a prediction of a 28% reduction in population numbers. For fathead minnows the DDE model predicts that the same concentration of NP could cause a population reduction of 21%. The differences in these predictions are related to these two species having different life history strategies, which are considered in the parameterization of the model. Post-application concentrations of MXC may peak around 300?µg l^?1 and then decline rapidly with time. Predictions show that such applications could cause a reduction of up to 30% in brook trout populations if the application occurs at the peak of the spawning season on successive years but that the effect would be less than 1% if the spawning season is avoided. Effects on the fathead minnow population size are predicted to be smaller (<4%) even if application occurs during the spawning period. Risk based statistics generated by the population dynamics models, such as interval decline risk or quasiextinction risk and predicted time to recovery complement traditional effects parameters such as LC50 and LOEC and may ultimately prove to be more useful in risk assessment.